Decreased lesion formation in CCR2−/− mice reveals a role for chemokines in the initiation of atherosclerosis
Chemokines are proinflammatory cytokines that function in leukocyte chemoattraction and activation and have recently been shown to block the HIV-1 infection of target cells through interactions with chemokine receptors 1 , 2 . In addition to their function in viral disease, chemokines have been impl...
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| Veröffentlicht in: | Nature (London) 1998-08, Vol.394 (6696), p.894-897 |
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| creator | Boring, Landin Gosling, Jennifa Cleary, Michael Charo, Israel F. |
| description | Chemokines are proinflammatory cytokines that function in leukocyte chemoattraction and activation and have recently been shown to block the HIV-1 infection of target cells through interactions with chemokine receptors
1
,
2
. In addition to their function in viral disease, chemokines have been implicated in the pathogenesis of atherosclerosis. Expression of the CC chemokine monocyte chemoattractant protein-1 (MCP-1) is upregulated in human atherosclerotic plaques
3
,
4
, in arteries of primates on a hypercholesterolaemic diet
5
and in vascular endothelial and smooth muscle cells exposed to minimally modified lipids
5
,
6
. To determine whether MCP-1 is causally related to the development of atherosclerosis, we generated mice that lack CCR2, the receptor for MCP-1 (
ref. 7
), and crossed them with apolipoprotein (apo) E-null mice
8
,
9
,
10
which develop severe atherosclerosis. Here we show that the selective absence of CCR2 decreases lesion formation markedly in apoE
−/−
mice but has no effect on plasma lipid or lipoprotein concentrations. These data reveal a role for MCP-1 in the development of early atherosclerotic lesions and suggest that upregulation of this chemokine by minimally oxidized lipids is an important link between hyperlipidaemia and fatty streak formation. |
| doi_str_mv | 10.1038/29788 |
| format | Article |
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1
,
2
. In addition to their function in viral disease, chemokines have been implicated in the pathogenesis of atherosclerosis. Expression of the CC chemokine monocyte chemoattractant protein-1 (MCP-1) is upregulated in human atherosclerotic plaques
3
,
4
, in arteries of primates on a hypercholesterolaemic diet
5
and in vascular endothelial and smooth muscle cells exposed to minimally modified lipids
5
,
6
. To determine whether MCP-1 is causally related to the development of atherosclerosis, we generated mice that lack CCR2, the receptor for MCP-1 (
ref. 7
), and crossed them with apolipoprotein (apo) E-null mice
8
,
9
,
10
which develop severe atherosclerosis. Here we show that the selective absence of CCR2 decreases lesion formation markedly in apoE
−/−
mice but has no effect on plasma lipid or lipoprotein concentrations. These data reveal a role for MCP-1 in the development of early atherosclerotic lesions and suggest that upregulation of this chemokine by minimally oxidized lipids is an important link between hyperlipidaemia and fatty streak formation.</description><identifier>ISSN: 0028-0836</identifier><identifier>EISSN: 1476-4687</identifier><identifier>DOI: 10.1038/29788</identifier><identifier>PMID: 9732872</identifier><identifier>CODEN: NATUAS</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>AIDS/HIV ; Animals ; Aorta - pathology ; Apolipoproteins E - physiology ; Arteriosclerosis - blood ; Arteriosclerosis - etiology ; Arteriosclerosis - pathology ; Atherosclerosis (general aspects, experimental research) ; Biological and medical sciences ; Blood and lymphatic vessels ; Cardiology. Vascular system ; Cardiovascular disease ; Chemokine CCL2 - physiology ; Cholesterol - blood ; Diet, Atherogenic ; Humanities and Social Sciences ; Lesions ; letter ; Lipids ; Lipoproteins - blood ; Medical research ; Medical sciences ; Mice ; Mice, Inbred C57BL ; multidisciplinary ; Myocardium - pathology ; Proteins ; Receptors, CCR2 ; Receptors, Chemokine - physiology ; Receptors, Cytokine - genetics ; Receptors, Cytokine - physiology ; Science ; Science (multidisciplinary) ; Triglycerides - blood ; Viral diseases</subject><ispartof>Nature (London), 1998-08, Vol.394 (6696), p.894-897</ispartof><rights>Macmillan Magazines Ltd. 1998</rights><rights>1998 INIST-CNRS</rights><rights>Copyright Macmillan Journals Ltd. Aug 27, 1998</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c457t-68d47d5eb67e6f16912f33e4ed8bca4a4420eecf82f24c9dd9e565415e1ad6173</citedby><cites>FETCH-LOGICAL-c457t-68d47d5eb67e6f16912f33e4ed8bca4a4420eecf82f24c9dd9e565415e1ad6173</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/29788$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/29788$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=2364234$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9732872$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Boring, Landin</creatorcontrib><creatorcontrib>Gosling, Jennifa</creatorcontrib><creatorcontrib>Cleary, Michael</creatorcontrib><creatorcontrib>Charo, Israel F.</creatorcontrib><title>Decreased lesion formation in CCR2−/− mice reveals a role for chemokines in the initiation of atherosclerosis</title><title>Nature (London)</title><addtitle>Nature</addtitle><addtitle>Nature</addtitle><description>Chemokines are proinflammatory cytokines that function in leukocyte chemoattraction and activation and have recently been shown to block the HIV-1 infection of target cells through interactions with chemokine receptors
1
,
2
. In addition to their function in viral disease, chemokines have been implicated in the pathogenesis of atherosclerosis. Expression of the CC chemokine monocyte chemoattractant protein-1 (MCP-1) is upregulated in human atherosclerotic plaques
3
,
4
, in arteries of primates on a hypercholesterolaemic diet
5
and in vascular endothelial and smooth muscle cells exposed to minimally modified lipids
5
,
6
. To determine whether MCP-1 is causally related to the development of atherosclerosis, we generated mice that lack CCR2, the receptor for MCP-1 (
ref. 7
), and crossed them with apolipoprotein (apo) E-null mice
8
,
9
,
10
which develop severe atherosclerosis. Here we show that the selective absence of CCR2 decreases lesion formation markedly in apoE
−/−
mice but has no effect on plasma lipid or lipoprotein concentrations. These data reveal a role for MCP-1 in the development of early atherosclerotic lesions and suggest that upregulation of this chemokine by minimally oxidized lipids is an important link between hyperlipidaemia and fatty streak formation.</description><subject>AIDS/HIV</subject><subject>Animals</subject><subject>Aorta - pathology</subject><subject>Apolipoproteins E - physiology</subject><subject>Arteriosclerosis - blood</subject><subject>Arteriosclerosis - etiology</subject><subject>Arteriosclerosis - pathology</subject><subject>Atherosclerosis (general aspects, experimental research)</subject><subject>Biological and medical sciences</subject><subject>Blood and lymphatic vessels</subject><subject>Cardiology. Vascular system</subject><subject>Cardiovascular disease</subject><subject>Chemokine CCL2 - physiology</subject><subject>Cholesterol - blood</subject><subject>Diet, Atherogenic</subject><subject>Humanities and Social Sciences</subject><subject>Lesions</subject><subject>letter</subject><subject>Lipids</subject><subject>Lipoproteins - blood</subject><subject>Medical research</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>multidisciplinary</subject><subject>Myocardium - pathology</subject><subject>Proteins</subject><subject>Receptors, CCR2</subject><subject>Receptors, Chemokine - physiology</subject><subject>Receptors, Cytokine - genetics</subject><subject>Receptors, Cytokine - physiology</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Triglycerides - blood</subject><subject>Viral diseases</subject><issn>0028-0836</issn><issn>1476-4687</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BEC</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp9kd1KHTEUhUNR7PHnEQpBrL0azX8yl3K0VRCEUq-HnMxOjZ2ZaDKn4Bt47SP6JM14Dkq98CLZIevLyt4shPYoOaKEm2NWa2M-oRkVWlVCGb2BZoQwUxHD1We0nfMtIURSLbbQVq05M5rN0P0puAQ2Q4s7yCEO2MfU23E6hQHP5z_Z8-PTcVm4Dw5wgr9gu4wtTrGDCcbuBvr4JwyQpxfjDZQSxrDyiB7bcpVidt20h7yLNn1xgL113UHX389-zc-ry6sfF_OTy8oJqcdKmVboVsJCaVCeqpoyzzkIaM3CWWGFYATAecM8E65u2xqkkoJKoLZVVPMd9G3le5fi_RLy2PQhO-g6O0Bc5kYLThWVL-ThxyQ3RlJJCrj_DryNyzSUKRpGhNCc6snt6wpyZdycwDd3KfQ2PTSUNFNSzUtShfuyNlsuemhfqXU0RT9Y6zY72_lkBxfyK8a4EoyLt-ZzUYbfkN56-v-_f0LZp70</recordid><startdate>19980827</startdate><enddate>19980827</enddate><creator>Boring, Landin</creator><creator>Gosling, Jennifa</creator><creator>Cleary, Michael</creator><creator>Charo, Israel F.</creator><general>Nature Publishing Group UK</general><general>Nature Publishing</general><general>Nature Publishing Group</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7ST</scope><scope>7T5</scope><scope>7TG</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88G</scope><scope>88I</scope><scope>8AF</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BEC</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>BKSAR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>M2O</scope><scope>M2P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PCBAR</scope><scope>PDBOC</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PSYQQ</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>Q9U</scope><scope>R05</scope><scope>RC3</scope><scope>S0X</scope><scope>SOI</scope><scope>7X8</scope><scope>7SC</scope><scope>7SP</scope><scope>7SR</scope><scope>7TB</scope><scope>7U5</scope><scope>8BQ</scope><scope>F28</scope><scope>JG9</scope><scope>JQ2</scope><scope>KR7</scope><scope>L7M</scope><scope>L~C</scope><scope>L~D</scope></search><sort><creationdate>19980827</creationdate><title>Decreased lesion formation in CCR2−/− mice reveals a role for chemokines in the initiation of atherosclerosis</title><author>Boring, Landin ; Gosling, Jennifa ; Cleary, Michael ; Charo, Israel F.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c457t-68d47d5eb67e6f16912f33e4ed8bca4a4420eecf82f24c9dd9e565415e1ad6173</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1998</creationdate><topic>AIDS/HIV</topic><topic>Animals</topic><topic>Aorta - pathology</topic><topic>Apolipoproteins E - physiology</topic><topic>Arteriosclerosis - blood</topic><topic>Arteriosclerosis - etiology</topic><topic>Arteriosclerosis - pathology</topic><topic>Atherosclerosis (general aspects, experimental research)</topic><topic>Biological and medical sciences</topic><topic>Blood and lymphatic vessels</topic><topic>Cardiology. Vascular system</topic><topic>Cardiovascular disease</topic><topic>Chemokine CCL2 - physiology</topic><topic>Cholesterol - blood</topic><topic>Diet, Atherogenic</topic><topic>Humanities and Social Sciences</topic><topic>Lesions</topic><topic>letter</topic><topic>Lipids</topic><topic>Lipoproteins - blood</topic><topic>Medical research</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>multidisciplinary</topic><topic>Myocardium - pathology</topic><topic>Proteins</topic><topic>Receptors, CCR2</topic><topic>Receptors, Chemokine - physiology</topic><topic>Receptors, Cytokine - genetics</topic><topic>Receptors, Cytokine - physiology</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>Triglycerides - blood</topic><topic>Viral diseases</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Boring, Landin</creatorcontrib><creatorcontrib>Gosling, Jennifa</creatorcontrib><creatorcontrib>Cleary, Michael</creatorcontrib><creatorcontrib>Charo, Israel F.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Environment Abstracts</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>Science Database (Alumni Edition)</collection><collection>STEM Database</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>eLibrary</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Earth, Atmospheric & Aquatic Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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Academic</collection><collection>Computer and Information Systems Abstracts</collection><collection>Electronics & Communications Abstracts</collection><collection>Engineered Materials Abstracts</collection><collection>Mechanical & Transportation Engineering Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>METADEX</collection><collection>ANTE: Abstracts in New Technology & Engineering</collection><collection>Materials Research Database</collection><collection>ProQuest Computer Science Collection</collection><collection>Civil Engineering Abstracts</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>Computer and Information Systems Abstracts Academic</collection><collection>Computer and Information Systems Abstracts Professional</collection><jtitle>Nature (London)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Boring, Landin</au><au>Gosling, Jennifa</au><au>Cleary, Michael</au><au>Charo, Israel F.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Decreased lesion formation in CCR2−/− mice reveals a role for chemokines in the initiation of atherosclerosis</atitle><jtitle>Nature (London)</jtitle><stitle>Nature</stitle><addtitle>Nature</addtitle><date>1998-08-27</date><risdate>1998</risdate><volume>394</volume><issue>6696</issue><spage>894</spage><epage>897</epage><pages>894-897</pages><issn>0028-0836</issn><eissn>1476-4687</eissn><coden>NATUAS</coden><abstract>Chemokines are proinflammatory cytokines that function in leukocyte chemoattraction and activation and have recently been shown to block the HIV-1 infection of target cells through interactions with chemokine receptors
1
,
2
. In addition to their function in viral disease, chemokines have been implicated in the pathogenesis of atherosclerosis. Expression of the CC chemokine monocyte chemoattractant protein-1 (MCP-1) is upregulated in human atherosclerotic plaques
3
,
4
, in arteries of primates on a hypercholesterolaemic diet
5
and in vascular endothelial and smooth muscle cells exposed to minimally modified lipids
5
,
6
. To determine whether MCP-1 is causally related to the development of atherosclerosis, we generated mice that lack CCR2, the receptor for MCP-1 (
ref. 7
), and crossed them with apolipoprotein (apo) E-null mice
8
,
9
,
10
which develop severe atherosclerosis. Here we show that the selective absence of CCR2 decreases lesion formation markedly in apoE
−/−
mice but has no effect on plasma lipid or lipoprotein concentrations. These data reveal a role for MCP-1 in the development of early atherosclerotic lesions and suggest that upregulation of this chemokine by minimally oxidized lipids is an important link between hyperlipidaemia and fatty streak formation.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>9732872</pmid><doi>10.1038/29788</doi><tpages>4</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0028-0836 |
| ispartof | Nature (London), 1998-08, Vol.394 (6696), p.894-897 |
| issn | 0028-0836 1476-4687 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_743161517 |
| source | MEDLINE; Springer Online Journals Complete; Nature Journals Online |
| subjects | AIDS/HIV Animals Aorta - pathology Apolipoproteins E - physiology Arteriosclerosis - blood Arteriosclerosis - etiology Arteriosclerosis - pathology Atherosclerosis (general aspects, experimental research) Biological and medical sciences Blood and lymphatic vessels Cardiology. Vascular system Cardiovascular disease Chemokine CCL2 - physiology Cholesterol - blood Diet, Atherogenic Humanities and Social Sciences Lesions letter Lipids Lipoproteins - blood Medical research Medical sciences Mice Mice, Inbred C57BL multidisciplinary Myocardium - pathology Proteins Receptors, CCR2 Receptors, Chemokine - physiology Receptors, Cytokine - genetics Receptors, Cytokine - physiology Science Science (multidisciplinary) Triglycerides - blood Viral diseases |
| title | Decreased lesion formation in CCR2−/− mice reveals a role for chemokines in the initiation of atherosclerosis |
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